Endothelial dysfunction over the course of coronary artery disease

Abstract

The vascular endothelium regulates blood flow in response to physiological needs. Endothelial dysfunction is closely related to atherosclerosis and its risk factors, and it constitutes an intermediate step on the progression to adverse events throughout the natural history of coronary artery disease (CAD), often affecting clinical outcomes. Understanding the relation of endothelial function with CAD provides an important pathophysiological insight, which can be useful both in clinical and research management. In this review, we summarize the current knowledge on endothelial dysfunction and its prognostic influence throughout the natural history of CAD, from early atherosclerosis to post-transplant management.

Keywords: Acetylcholine; Coronary heart disease; Endothelial dysfunction; Heart failure; Heart transplant.

Figure 1

Endothelium-derived vasoactive substances. Shear stress and activation of a variety of receptors leads to a release of nitric oxide by inducing endothelial nitric oxide synthase. It exerts relaxation of vascular smooth muscle cells and exerts antiproliferative effects as well as inhibits thrombocyte aggregation and leucocyte adhesion. Other endothelium-derived relaxing factors, including endothelium-derived hyperpolarizing factor and prostacyclin, are also shown. ACE, angiotensin-converting enzyme; Ach, acetylcholine; AI, angiotensin I; AII, angiotensin II; AT1, angiotensin 1 receptor; Bk, bradykinin; COX, cyclooxygenase; ECE, ET-converting enzyme; EDHF, endothelium-derived hyperpolarizing factor; ETA and ETB, endothelin A and B receptors; ET-1, endothelin-1; l-Arg, l-arginine; M, muscarinic acetylcholine receptor; PGH2, prostaglandin H2; ROS, reactive oxygen species; S1, serotoninergic receptor; TX, thromboxane receptor; TXA2, thromboxane; 5-HT, serotonin. Reproduced with kind permission from Springer Science and Business Media. Source: Springer. Pflügers Arch- Eur J Physiol (2010) 459:1005–1013. Human endothelial dysfunction: EDRFs. Flammer and Lüscher.

Figure 2

Illustration of the reciprocal interaction between endothelial dysfunction, inflammation and the natural history of coronary artery disease. Blue arrows marked with the box ‘ED’ represent processes in which endothelial dysfunction modifies the evolution or prognosis of coronary artery disease. Red arrows represent ways in which coronary artery disease contributes to a worse endothelial function.

Figure 3

Illustration of the post-stent epicardial reactivity to acetylcholine in the various studies referenced in the text^–. The values express the change in coronary artery lumen diameter (%) to acetylcholine or exercise, measured by angiography; horizontal short lines represent average, and vertical bars standard deviation. The red vertical line separates drug-eluting stents from bare metal stents. As can be appreciated, patients with drug-eluting stents exhibit a vasoconstrictive response, while patients with bare metal stents have a roughly neutral vascular response. AEES, absorbable everolimus eluting scaffold; BMS, bare metal stent; PES, paclitaxel eluting stent; DES, drug eluting stent; SES, sirolimus eluting stent; ZES, zotarolimus eluting stent.